Cited by 54Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology Research

Noradrenergic Hypothesis Linking Neurodegeneration-Based Cognitive Decline and Astroglia

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Leanza, Giampiero, Gulino, Rosario, Zorec, Robert·2018·Frontiers in Molecular Neuroscience

Abstract

In the past, manipulation of the cholinergic system was seen as the most likely therapeutic for neurodegeneration-based cognitive decline in Alzheimer's disease (AD) (Whitehouse et al., 1982). However, targeting the noradrenergic system also seems a promising strategy, since more recent studies revealed that in post-mortem tissue from patients with AD and other neurodegenerative disorders there is a robust correlation between cognitive decline and loss of neurons from the Locus coeruleus (LC), a system with diffuse noradrenaline (NA) innervation in the central nervous system (CNS). Therefore, the hypothesis has been considered that increasing NA signaling in the CNS will prevent, or at least halt the progression of neurodegeneration and cognitive decline. A hallmark of the age- and neurodegeneration-related cognitive decline is reduced neurogenesis. We here discuss noradrenergic dysfunction in AD-related cognitive decline in humans and its potential involvement in AD pathology and disease progression. We also focus on animal models to allow the validation of the noradrenergic hypothesis of AD, including those based upon the immunotoxin-mediated ablation of LC based on saporin, a protein synthesis interfering agent, which offers selective and graded demise of LC neurons, Finally, we address how astrocytes, an abundant and functionally heterogeneous cell type of neuroglia maintaining homeostasis, may participate in the regulation of neurogenesis, a new strategy for preventing LC neuron loss.

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Crossref · 10.3389/fnmol.2018.00254

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  • Noradrenergic receptors are densely present on astrocytes, and their activation improves synaptic plasticity and hence learning and memory.

    “Further it is reported that noradrenergic receptors are densely present on the astrocytes, the activation of which improves synaptic plasticity and hence learning and memory [10].”

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Authors
Leanza, G., Gulino, R., & Zorec, R.
Affiliations
  • University of Catania (IT)
  • University of Ljubljana (SI)
Corresponding author
  • Leanza, Giampiero
  • Zorec, Robert
Venue
Frontiers in Molecular Neuroscience
Published
2018-07-27
Volume
11
Pages
254-254
ISSN
1662-5099 (ISSN-L)
OpenAlex
W2884618236
Cited by
54
References
171
Citations by year
2026: 3 · 2025: 8 · 2024: 4 · 2023: 8 · 2022: 4 · 2021: 10 · 2020: 8 · 2019: 8 · 2018: 1
FWCI
0.89
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Molecular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Beneficentia Stiftung
  • Javna Agencija za Raziskovalno Dejavnost RS (P3-310, J3-6789, J3-6790, J3-7605)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Alzheimer's disease, cognitive decline, locus coeruleus, norepinephrine, neurodegeneration, astrocytes, neurogenesis, saporin, animal models of Alzheimer's disease, cholinergic hypothesis

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